- Phosphorus pentachloride promoted gem-dichlorination of 2′- and 3′-deoxynucleosides
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Halogen substitution at various positions of canonical nucleosides has generated a number of bioactive structural variants. Herein, the synthesis of two unique series of sugar modified nucleosides bearing a gem-dichloro group is presented. The synthetic plan entails the controlled addition of phosphorus pentachloride to suitably protected 2′- or 3′-ketodeoxynucleoside intermediates as the key step, facilitating the rapid construction of such functionalized molecules. Under the same reaction conditions, the highest chemoselectivity was observed for the formation of 2′,2′-dichloro-2′,3′-dideoxynucleosides, while a competing 2′,3′-elimination process occurred in the case of the 3′,3′-dichloro counterparts.
- Da Paixao Soares, Fabio,Groaz, Elisabetta,Herdewijn, Piet
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Read Online
- Synthesis of 2-deoxy ribose related disaccharide nucleoside and its phosphoramidite
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Synthesis of impurity reference compound of anti-tumor drug ISIS 183750 was achieved. In this process, a general method for synthesis of 2-deoxy ribosyl disaccharide nucleosides was established for the first time.
- Ding, Yili,Deng, Rilie,Wang, Bingyun
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Read Online
- A new and easy synthesis of silylated furanoid glycals in one step from nucleotides
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Silylated furanoid glycals are synthesized in high yields by elimination of the nucleobase in thymidine (1a) and 5'-O-(tert-butyldiphenylsilyl)thymidine (1b) on treatment with 1,1,1,3,3,3-hexamethyldisilazane (HMDS) in the presence of ammonium sulfate at
- Larsen,Jorensen,Sofan,Pedersen
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Read Online
- Selective cleavage of O-(dimethoxytrityl) protecting group with sodium periodate
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Sodium periodate in aqueous organic solvents selectively removes, under mild reaction conditions, the O-(dimethoxytrityl) protecting group. Selectivity of the cleavage was studied using the nucleoside derivatives protected by various types of groups commonly used in nucleoside and nucleotide chemistry.
- Rejman, Dominik,Kralikova, Sarka,Tocik, Zdenek,Liboska, Radek,Rosenberg, Ivan
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Read Online
- REVERSIBLE TERMINATORS FOR DNA SEQUENCING AND METHODS OF USING THE SAME
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The present disclosure provides methods of sequencing polynucleotides and compounds, compositions for sequencing of polynucleotides, and synthesis of such compositions. The chemical compounds include nucleotides and their analogs which possess a sugar moiety comprising a cleavable chemical group capping the 3'-OH group and a base, but without covalently bounded dye. The cleavable chemical group is reactive to form covalent bond(s) with a dye used to confirm the presence of the expected base-pairing. The cleavable chemical group capping the 3'OH group can be removed together with the covalently bounded dye. Furthermore, after the cleavable chemical group is cleaved, the free 3'-OH group can be active in continued elongation. Example chemical compounds according to the present disclosure are shown as Formulas (II) and (V).
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Paragraph 0095-0096; 00183-00184
(2021/04/10)
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- MODIFIED NUCLEOTIDES AND USES THEREOF
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Disclosed herein, inter alia, are compounds, modified nucleotides, compositions, and methods of using the same.
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Paragraph 0401-0402; 0406
(2021/10/30)
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- NUCLEOTIDE CLEAVABLE LINKERS AND USES THEREOF
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Disclosed herein, inter alia, are compounds, compositions, and methods of use thereof for sequencing a nucleic acid.
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Paragraph 0776
(2020/07/26)
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- NOVEL PHOSPHOROUS (V)-BASED REAGENTS, PROCESSES FOR THE PREPARATION THEREOF, AND THEIR USE IN MAKING STEREO-DEFINED ORGANOPHOSHOROUS (V) COMPOUNDS
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The present invention relates to novel phosphorous (V) (P(V)) reagents, methods for preparing thereof, and methods for preparing organophosphorous (V) compounds by using the novel reagents.
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Paragraph 0313; 0317
(2019/11/04)
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- LINKAGE MODIFIED OLIGOMERIC COMPOUNDS
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The present invention provides gapped oligomeric compounds comprising from 1 to about 3 internucleoside linkages having one of formulas I to XVI. In certain embodiments, inclusion of from 1 to about 3 internucleoside linkages of one of formulas I to XVI,
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Page/Page column 77
(2020/01/11)
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- OLIGONUCLEOTIDE AND NUCLEIC ACID SYNTHESIS
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The present invention relates to methods for the high fidelity synthesis of oligonucleotides and polynucleotides on a solid surface. In particular, the invention relates to methods of synthesising oligonucleotides, polynucleotides, and doublestranded polynucleotides/nucleic acids, such as DNA and XNA, wherein the process comprises thermally controlled deprotection steps at the 5'-OH of previously coupled nucleosides or nucleotides at selected sites on the surface of the substrate.
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- THERMALLY-CLEAVABLE PROTECTING AND LINKER GROUPS
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The present invention relates to chemical linkers and protecting groups, compounds and compositions containing the chemical linkers or protecting groups, and intermediates and processes that can be used to prepare them. The chemical linkers and protecting groups are based on pyrrolidine and piperidine activating groups, which undergo intramolecular cyclisation upon heating with release of carbon dioxide, thereby releasing the organic compound from a substrate. In particular, those chemical linkers and protecting groups are useful in the solid phase synthesis of oligonucleotides according to the following representative schemes.
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- Practical and Reliable Synthesis of 1,2-Dideoxy-D-ribofuranose and its Application in RNAi Studies
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We developed a practical and reliable method for synthesizing an abasic deoxyribonucleoside, 1,2-dideoxy-D-ribofuranose (dRH) via elimination of nucleobase from thymidine. To synthesize oligonucleotides bearing dRH by the standard ph
- Nagaya, Yuki,Kitamura, Yoshiaki,Nakashima, Remi,Shibata, Aya,Ikeda, Masato,Kitade, Yukio
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- Tailoring peptide-nucleotide conjugates (PNCs) for nucleotide delivery in bacterial cells
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The design and synthesis of peptide-2′-deoxythymidine-5′-O- monophosphate conjugates as potential active delivery systems for nucleotides into auxotrophic E. coli strains is presented. A series of oligopeptides were allowed to react with 5′-O-(dibenzylphosphate)-2′-deoxythymidine or its suitably 3′-derivatized analogues to give the relevant peptide-nucleotide adducts, by the formation of a biolabile chemical connection. Using strategies based on the principles of orthogonal protection and activation, rational variations were made to the linker and the peptide moiety in order to tune the metabolic stability of the conjugates.
- De, Swarup,Groaz, Elisabetta,Herdewijn, Piet
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p. 2322 - 2348
(2014/04/17)
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- One-pot synthesis of β-N-glycosyl imidazole analogues via a palladium-catalysed decarboxylative allylation
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A concise and highly efficient strategy for the synthesis of N-glycosyl imidazole analogues is reported. This reaction is based on a palladium catalysed decarboxylative allylation and three steps, namely, carbamation, decarboxylation and allylation are involved. All the substrates can afford the desired products with excellent yields and selectivities. the Partner Organisations 2014.
- Xiang, Shaohua,He, Jingxi,Ma, Jimei,Liu, Xue-Wei
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supporting information
p. 4222 - 4224
(2014/04/17)
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- Crystal structures and repair studies reveal the identity and the base-pairing properties of the UV-induced spore photoproduct DNA lesion
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UV light is one of the major causes of DNA damage. In spore DNA, due to an unusual packing of the genetic material, a special spore photoproduct lesion (SP lesion) is formed, which is repaired by the enzyme spore photoproduct lyase (Spl), a radical S-adenosylmethionine (SAM) enzyme. We report here the synthesis and DNA incorporation of a DNA SP lesion analogue lacking the phosphodiester backbone. The oligonucleotides were used for repair studies and they were cocrystallized with a polymerase enzyme as a template to clarify the configuration of the SP lesion and to provide information about the base-pairing properties of the lesion. The structural analysis together with repair studies allowed us to clarify the identity of the preferentially repaired lesion diastereoisomer.
- Heil, Korbinian,Kneuttinger, Andrea Christa,Schneider, Sabine,Lischke, Ulrike,Carell, Thomas
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supporting information; experimental part
p. 9651 - 9657
(2011/10/02)
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- Synthesis of 3′-C-substituted thymidine derivatives by free-radical techniques: scope and limitations
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The scope and limitations of radical-mediated 3′-C-substitution of pyrimidine nucleosides was evaluated with 5′-O-(tert-butyldimethylsilyl)thymidine or its tert-butyldiphenylsilyl analogue having thionoester or thionoamide groups at O-3′, including (methy
- Horton, Derek,Chen, Kuangmin,No, Zaesung,Lee, Howard C.
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p. 259 - 267
(2007/10/03)
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- Synthesis, anti-HIV activity, and resistance profile of thymidine phosphonomethoxy nucleosides and their bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs
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Phosphonomethoxy nucleoside analogs of the thymine containing nucleoside reverse transcriptase inhibitors (NRTIs), 3′-azido-2′,3′-dideoxythymidine (AZT), 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), and 2′,3′-dideoxythymidine (ddT), were synthesized. The anti-HIV activity against wild-type and several major nucleoside-resistant strains of HIV-1 was evaluated together with the inhibition of wild-type HIV reverse transcriptase (RT). Phosphonomethoxy analog of d4T, 8 (d4TP), demonstrated antiviral activity with an EC50 value of 26 μM, whereas, phosphonomethoxy analogs of ddT, 7 (ddTP), and AZT, 6 (AZTP), were both inactive at concentrations up to 200 μM. Bis-isopropyloxymethylcarbonyl (bisPOC) prodrugs improved the anti-HIV activity of 7 and 8 by >150-fold and 29-fold, respectively, allowing for antiviral resistance to be determined. The K65R RT mutant virus was more resistant to the bisPOC prodrugs of 7 and 8 than bisPOC PMPA (tenofovir DF) 1. However, bisPOC prodrug of 7 demonstrated superior resistance toward the RT virus containing multiple thymidine analog mutations (6TAMs) indicating that new phosphonate nucleoside analogs may be suitable for targeting clinically relevant nucleoside resistant HIV-1 strains.
- Mackman, Richard L.,Zhang, Lijun,Prasad, Vidya,Boojamra, Constantine G.,Douglas, Janet,Grant, Deborah,Hui, Hon,Kim, Choung U.,Laflamme, Genevieve,Parrish, Jay,Stoycheva, Antitsa D.,Swaminathan, Swami,Wang, KeYu,Cihlar, Tomas
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p. 5519 - 5528
(2008/03/14)
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- Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: A comparison of phosphonates and corresponding nucleosides
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Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T, and ddC have been synthesized. The RT inhibitory activities of the phosphonates were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity. Copyright Taylor & Francis Group, LLC.
- Mackman, Richard L.,Zhang, Lijun,Prasad, Vidya,Boojamra, Constantine G.,Chen, James,Douglas, Janet,Grant, Deborah,Laflamme, Genevieve,Hui, Hon,Kim, Choung U.,Parrish, Jay,Stoycheva, Antitsa D.,Swaminathan, Swami,Wang, KeYu,Cihlar, Tomas
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p. 573 - 577
(2008/09/17)
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- Nucleosidyl-O-methylphosphonates: A pool of monomers for modified oligonucleotides
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An unique set of 5′-O- and 3′-O-phosphonomethyl derivatives of four natural 2′-deoxyribonucleosides, 1-(2-deoxy-β-D-threo- pentofuranosyl)thymine, 5′-O- and 2′-O-phosphonomethyl derivatives of 1-(3-deoxy-β-D-erythro-pentofuranosyl)thymine, and 1-(3-deoxy-β-D- threo-pentofuranosyl)thymine has been synthesized as a pool of monomers for the synthesis of modified oligonucleotides. The phosphonate moiety was protected with 4-methoxy-1-oxido-2-pyridylmethyl ester group, serving also as an intramolecular catalyst in the coupling step.
- Rejman, Dominik,Masojidkova, Milena,Rosenberg, Ivan
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p. 1683 - 1705
(2007/10/03)
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- Synthesis and Antiviral Activity of Novel Fluorinated 2′,3′ -Dideoxynucleosides
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A series of 5-(trifluoroethoxymethyl)-2′,3′-dideoxyuridines and 5-[bis(trifluormethoxy)-methyl]-2′,3′-dideoxyuridines have been prepared and screened for antiviral activity. The conformations of these compounds are discussed on the bases of NOE studies and the MO calculations. Modelling and NOE studies suggest both syn- and anti conformations for these 5-(2,2,2-trifluoroethoxymethyl)- and 5-[bis(2,2,2-trifluoroethoxy)-methyl]-derivatives. The NOE parameters are also suggested to be more attributable to the nature of the fluorine atom than to structural or conformational changes. Compounds 17, 26 and 30 showed some activity in anti-HIV-1 and anti-HIV-2 assays, but the compounds were devoid of activity against HSV and human rhinovirus. The compounds tested exhibited low cytotoxicity and were inactive against a bank of cancer cells in vitro.
- Kumar, Piyush,Ohkura, Kazue,Balzarini, Jan,De Clercq, Erik,Seki, Koh-Ichi,Wiebe, Leonard I.
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- Nucleoside homodimerisation by cross metathesis
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The cross metathesis of 3′-allylic analogues of thymidine, 2′-deoxyuridine and 2′-deoxycytidine is used to obtain nucleoside dimers, in which an unsaturated hydrocarbon chain links the 3′ positions of the sugar moieties. The biological activity on HIV inf
- Batoux, Nathalie,Benhaddou-Zerrouki, Rachida,Bressolier, Philippe,Granet, Robert,Laumont, Géraldine,Aubertin, Anne-Marie,Krausz, Pierre
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p. 1491 - 1493
(2007/10/03)
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- Synthesis of thymidine dimer containing novel (N-acetyl)imino linkage
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By starting with 3′-keto-5′-O-protected thymidine, 3′-O-amino-5′-t-butyl-diphenylsilyl thymidine (9) was prepared and coupled with 3′-O-t-butyl-diphenylsilyl-5′-formyl thymidine to form a nucleoside dimer (11) containing oxime linkage. The backbone of thi
- Yang, Te-Fang,Chien, Fang-Chi,Chung, Fen-Yu
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p. 949 - 952
(2007/10/03)
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- Syntheses, crystal structures, and hydrogen bonding patterns of 3'-C- methylenecarboxylic-3'-deoxythymidine and 3'-C-methyleneamidilylic-3'- deoxythymidine
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Thymidine derivatives containing carboxylic acid and amide groups have been synthesized and the hydrogen-bonding patterns of 3'-C- methylenecarboxylic-3'-deoxythymidine 6 and 3'-C-methyleneamidilylic-3'- deoxythymidine 9 have been characterized by using X-ray crystallography.
- Kim, Joong Young,Kim, Byeang Hyean
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p. 637 - 650
(2007/10/03)
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- Diastereoselective synthesis of α-substituted-γ-butyrolactones of nucleosides via [1,5]-c,h insertion reactions of α-diazomalonates of nucleosides
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Diastereoselective and regioselective [1,5]-C,H insertion reactions of 2'-deoxy-3'-diazomalonate nucleosides afforded τ-butyrolactones of nucleosides as chiral synthons for the preparation of 2'-C-branched nucleosides.
- Lim, Jinsoo,Choo, Dong-Joon,Kim, Yong Hae
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p. 553 - 554
(2007/10/03)
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- Heteroatomic oligonucleoside linkages
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PCT No. PCT/US94/03536 Sec. 371 Date Sep. 18, 1995 Sec. 102(e) Date Sep. 18, 1995 PCT Filed Mar. 30, 1994 PCT Pub. No. WO94/22886 PCT Pub. Date Oct. 13, 1994Oligonucleotide-mimicking macromolecules that have improved nuclease resistance are provided. Repl
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- Nucleomimetic strategy for the inhibition of HIV-1 nucleocapsid protein NCp7 activities
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We report the synthesis and biological properties of three modified dinucleotides T*G G*T and T*T in which the natural phosphodiester linkage has been replaced by a methylene carboxamide unit. They have been designed to act as nucleomimetics of a sequence
- Druillennec, Sabine,Meudal, Herve,Roques, Bernard P.,Fournie-Zaluski, Marie-Claude
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p. 627 - 632
(2007/10/03)
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- 4'-desmethyl nucleoside analogs, and oligomers thereof
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Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnostic assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.
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- Solid-phase synthesis of branched RNA and branched DNA/RNA chimeras
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An effective method for synthesising branched oligonucleotides on solid phase in the 5' to 3' direction has been developed. Special branch-point monomers enable the synthesis of branched oligonucleotides which can have sequences of different length and base composition attached to the 2'- and 3'-hydroxyl groups of the branch point ribonucleoside. The branched oligonucleotides are assembled on commercial DNA synthesisers, the crude products are readily purified by reversed phase HPLC and the fully deprotected products are conveniently analysed by mass spectrometry.
- Grotli, Morten,Eritja, Ramon,Sproat, Brian
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p. 11317 - 11346
(2007/10/03)
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- Facile preparation of protected furanoid glycals from thymidine
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The synthesis of O-silyl- and O-acyl-protected furanose glycals from free thymidine was investigated. The method of glycal formation reported by Pedersen et al. was successfully expanded to include 5-ester (toluoyl) protected glycals as well as various combinations of 5'-ester and 3- and 5- tert-butyldimethylsilyl and tert-butyldiphenylsilyl protection. Gram quantities of furanoid glycals can be prepared in a few days in two-four steps in overall yields ranging from 17 to 80%.
- Cameron, Melissa A.,Cush, Sarah B.,Hammer, Robert P.
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p. 9065 - 9069
(2007/10/03)
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- Modified oligodeoxyribonucleoditides
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Compounds for the treatment or prophylaxis of a viral infection in a mammal, which may be human, are provided. The compounds are oligodeoxyribonucleic acid derivatives, and a novel route to such compounds is also provided together with intermediates of mo
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- Conjugated 4'-desmethyl nucleoside analog compounds
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Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnostic assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.
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- Methods of making conjugated 4' desmethyl nucleoside analog compounds
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Tetrahydrofuranyl compounds are provided that are functionalized to include pendant conjugate groups, and which are useful in diagnostic assays and as research reagents. Novel intermediates for the synthesis of the compounds are also provided.
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- An approach to photolabile, fluorescent protecting groups
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The photolablie and fluorescent system 1 was prepared via a convergent route which involved thymidine 3'-functionalized with a proline residue. Photodecomposition of 1 was examined using 360 nm irradiation. Without any additives, 5'-silylated thymidine was not formed, but the N(α)-deprotected cyclization precursor II accumulated instead. However, in the presence of ethanolamine, 5'-silylated thymidine formed at a rate which increases with the concentration of ethanolamine.
- Burgess,Jacutin,Lim,Shitangkoon
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p. 5165 - 5168
(2007/10/03)
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- Ribosylation of pyrimidine 2'-deoxynucleosides
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The previously developed method for the preparation of 2'-O-D- ribofuranosyl-nucleosides is extended to ribosylation of 2'- deoxynucleosides. The scope and limitations of this reaction are discussed.
- Mikhailov, Sergey N.,De Clercq, Erik,Herdewijn, Piet
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p. 1323 - 1334
(2007/10/03)
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- Efficient and stereoselective synthesis of 3'-deoxy 3'-C-branched-chain substituted thymidine
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In this report, we provide for the first time a facile, efficient, and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-3-C-formyl-β-D-erythro-p entofuranosyl]thymine (12), using an intermolecular radical C-C bond formation reacti
- Sanghvi,Bharadwaj,Debart,De Mesmaeker
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p. 1163 - 1166
(2007/10/02)
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- Photochemistry of di(deoxyribonucleoside) methylphosphonates containing N3-methyl-4-thiothymine
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(Rp)- and (Sp)-5'-N3-methyl-4-thiothymidine 3'-(thymidinyl methylphosphonate) (Tpm3s4T) (11a and 11b), respectively, have been synthesized in order to elucidate their photochemical behavior in comparison with that of their
- Clivio,Fourrey,Szabo,Stawinski
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p. 7273 - 7283
(2007/10/02)
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- Biologically active oligodeoxyribonucleotides - II: Structure activity relationships of anti-HIV-1 pentadecadeoxyribonucleotides bearing 5'-end- modifications
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5'-End-modified pentadecadeoxyribonucleotides (15mers) with a sequence complementary to the tat 2nd splicing acceptor region of human immunodeficiency virus type 1 (HIV-1) were prepared and evaluated for anti- HIV-1 activity. The structures of modified 15
- Hotoda,Momota,Furukawa,Nakamura,Kaneko,Kimura,Shimada
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p. 1375 - 1395
(2007/10/02)
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- New synthetic 'tricks'. Trimethylsilyl triflate mediated cleavage of hindered silyl ethers
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An alternative, mild procedure for the cleavage of t-butyldimethylsilyl and triphenylsilyl ethers to alcohols is shown, which is based on an exchange reaction with trimethylsilyl triflate below 0°C. t-Butyldiphenylsilyl groups are not removed under these
- Bou,Vilarrasa
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p. 567 - 568
(2007/10/02)
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- Nucleosides of 5-monofluoromethyluracil and 5-difluoromethyluracil
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A method for synthesizing monofluoromethyl- and difluoromethyluracil nucleosides from the corresponding thymine nucleosides is developed. These compounds which contain a partially fluorinated methyl group at the C-5 position (a new class of nucleosides) a
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- Synthesis of 2'-Deoxy-5-monofluoromethyluridine (FTDR) and 2'-Deoxy-5-difluoromethyluridine (F2TDR)
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The synthesis of potential anticancer and antitumour nucleosides, 2'-deoxy-5-monofluoromethyluridine (FTDR) and 2'-deoxy-5-difluoromethyluridine (F2TDR) was achieved in four steps from thymidine including monosilylation with t-butyldiphenylsilyl chloride,
- Matulic-Adamic, Jasenka,Watanabe, Kyoichi A.
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p. 1535 - 1536
(2007/10/02)
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